Different patterns of behavior produced by haloperidol, pentobarbital, and dantrolene in tests of unconditioned locomotion and operant responding

Abstract

Three motor-impairing drugs with different putative mechanisms of action (haloperidol 0.00, 0.075, 0.15, 0.30 mg/kg IP; pentobarbital 0.00, 4.5, 9, 12 mg/kg IP; and dantrolene 0.00, 5, 7.5, 10 mg/kg IP) produced strikingly similar patterns of dose-dependent attenuation in unconditioned locomotor behavior. However, the same drugs and doses produced highly divergent patterns of disruption when tested using different groups of rats in a food-rewarded operant task, which included both response initiation and maintenance components (FR1-FR1 two lever chain). Haloperidol animals began the session as fast as vehicle animals and slowed dose-dependently across trials; pentobarbital animals started off significantly slower than controls but soon achieved comparable speeds; and dantrolene animals were slower throughout the session. These results suggest that the observed neuroleptic-induced deterioration in responding over trials, especially in response initiation, was not simply a result of motoric disruption. Rather, the profile of this deterioration is consistent with the anhedonia hypothesis of neuroleptic action and supports the view that dopamine neurons are involved in the biological basis of food reward.